1. ABSTRACT The islets of Langerhans are ordered assemblies of different endocrine cell types which interact one with the others to maintain an optimal hormonal output. Junctional-mediated exchanges of ions and molecules (ionic and metabolic coupling) between islet cells may play a role in the control of such an integrated activity. To test this hypothesis, a combined morphological and physiological study of coupling and secretion of insulin-producing B-cells is proposed. We plan to characterize the membrane specializations mediating B-cell coupling, by quantitating the development and structure of gap and tight junctions, as revealed by freeze-fracture in isolated rat islets, and to determine how these correlate with secretory events and intercellular exhanges of ions and molecules. The occurrence and regulation of direct molecular exchanges between B-cells as well as between B- and non B-cells, will be studied, under different conditions of insulin secretion, by following the transfer of fluorescent and radioactive molecules, introduced in endocrine islet cells either in culture or within whole islets. Ionic exchanges will be followed by electrophysiology in the same systems. Both morphological and physiological studies will be carried out on islets from control and experimental diabetic rats to assess whether hormonal abnormalities precede or follow perturbations of islet cell coupling. This approach is designed to provide new information on both the control of B-cell secretion and the function of B-cell coupling. Hopefully, this will help to understand the pathogenesis of certain forms of diabetes, which may be attributable to faulty communication among islet cells.